Background: There is no study focusing on changes in coronary atherosclerosis during dual lipid-lowering therapy with statin and ezetimibe. Methods and Results: Eighty-nine patients with stable angina randomized in a 1:1 ratio to Group A (aggressive therapy: atorvastatin 80mg, ezetimibe 10mg) and Group S (standard therapy) were analyzed. Treatment period was 12 months. Coronary arteries were examined by intravascular ultrasound and virtual histology. We found a decrease in the percent atheroma volume (PAV) (-0.4%) in Group A compared with an increase (+1.4%) in Group S (P=0.014) and this was accompanied by an increased frequency of combined atherosclerosis regression (increased lumen volume+decreased PAV) in group A (40.5%) compared with group S (14.9%) (P=0.007). The target low-density lipoprotein cholesterol level <2mmol/L, presence of at least 4 of 5 atherosclerotic risk factors, and decreased level of vascular cellular adhesive molecule were independent predictors of plaque regression. There were no significant differences in plaque composition between the 2 groups over the study duration. However, during analysis of the 2 groups together, fibrous and fibro-fatty tissues decreased and dense calcification and necrotic core increased during follow-up. Conclusions: Dual lipid-lowering therapy starts atherosclerosis regression, but does not lead to significant changes in plaque composition. The continuous shift in plaque from fibro and fibro-fatty to necrotic with calcification was present in both groups.